In gene therapy, genetic information is delivered to a host cell in order to either correct (supplement) a genetic deficiency in the cell, or to inhibit an unwanted function in the cell, or to eliminate the host cell. Of course the genetic information can also be intended to provide the host cell with a wanted function, for instance to supply a secreted protein to treat other cells of the host, etc.
Thus, there are basically three different approaches in gene therapy, one directed towards compensating a deficiency present in a (mammalian) host; the second directed towards the removal or elimination of unwanted substances (organisms or cells) and the third towards providing a cell with a wanted function.
In order to provide cells with a gene (nucleic acid) of interest for any of the purposes identified above, a vehicle capable of delivering the gene to a host cell in a functional format is necessary. In certain instances transient expression (up to a number of weeks or somewhat longer) is desired, in others permanent transduction of a host cell seems necessary. In order to achieve these goals various vehicles are available. Retroviruses and adeno associated viruses are capable of integrating their genome (including a gene (nucleic acid) of interest) into the genome of a host cell, adenoviruses remain episomal. However, adenoviruses are better capable of infecting many kinds of cells, since retrovirus only infects certain specific cells. Combinations of different viruses (chimeric viruses) have been proposed to use the advantages of different kinds of viruses.
Of course, non-viral delivery systems are also available as are synthetic viruses, all of which can also be adapted to the specific target at hand. All of these systems may be applied in the hereinafter described invention.
It is known that stem cells are typically difficult to infect to a significant extent with the gene delivery vehicles of the prior art. If infection succeeds, functional expression, especially over a significant amount of time has been difficult to achieve. The infection of stem cells has been considered one of the more disappointing aspects of gene therapy.